Metaplastic Carcinoma of Breast with Osteosarcomatous Differentiation: A Rare Case Diagnosed by Fine Needle Aspiration Cytology

Invasive breast cancer with osseous metaplasia is rare. Here we report two cases of metaplastic breast carcinoma with extensive osseous differentiation. Case 1: The patient was a 60-year-old woman with a right breast tumor, about 4 cm in diameter. Mammogram and ultrasound presented an irregular-shaped mass suspected for malignancy. Core needle biopsy confirmed invasive carcinoma and the patient underwent a modified radical mastectomy. Case 2: The patient was a 48-year-old woman with a left breast tumor, about 3 cm in diameter. Mammogram demonstrated a well-circumscribed mass with extensive dense calcifications. Frozen section biopsy confirmed invasive carcinoma and a modified radical mastectomy was performed. The two patients had no metastatic carcinoma in the axillary lymph nodes and remained free of recurrence and systemic metastases in a 13- and 4-month follow-up period, respectively. Histopathologically, patient 1 had an adenocarcinoma with prominent sarcomatous (osteosarcomatous) differentiation with intervening spindle cells. The sarcomatous areas showed high nuclear atypia, pleomorphism and a high Ki-67 index. In Case 2, the neoplasm consisted of invasive ductal carcinoma of no special type with an osseous metaplasia component and showed a direct transition from the carcinoma to the osseous elements. The distinction between the different types of metaplastic carcinomas, specifically the distinction between benign and malignant metaplastic (osteoid) elements, should be taken into consideration.

INTRODUCTION: Metaplastic breast carcinoma is a rare condition, representing less than 1% of the invasive carcinomas of the breast. These tumors, in addition to the carcinomatous component, are constituted by mesenchymal, fusocellular and squamous dominant elements. They are characterized by a high growth rate, aggression and immunohistochemical characteristics of the basal-like carcinomas of the breast (triple negative). REPORT: An eighty six years old lady, first seen at September 2011, at the Breast Surgery Department at Hospital das Clinicas, Universidade Federal de Minas Gerais, Brazil. She had a complaint of a palpable mass at her right breast. On her physical exam there was palpable mass of 5 cm at her right breast, extending to the axilla, consistent of a clinical staging of T4bN0M0. Her mammogram showed a spiculated nodule in axillary tail of Spence at the right breast, BIRADSTM 5. Her breast ultrasound showed a spiculated hypoechoic nodule of 3. 6 cm at the outer quadrant of her right breast, BIRADSTM 5. Incisional biopsy was performed, positive for a spindle cell neoplasm with a low mitotic index - this could represent a mesenchymal (fibrosarcoma) or mammary neoplasm (myofibroblastoma or spindle cell metaplastic carcinoma). Immunohistochemistry was positive for a metaplastic spindle cell carcinoma. Family at first did not allow the surgical procedure, which delayed her treatment. When authorized by the family, surgery was performed in March 2012 and she underwent a radical modified mastectomy. Her pathological findings were: metaplastic breast carcinoma type fibrosarcoma with mild cell pleomorphism, low histological grade, skin infiltrated by contiguity and free surgical margins. pT3(5, 5)N0(0/10)M0. New immunohistochemistry was performed at the surgical specimen compatible with a metaplastic spindle cell carcinoma (staining strongly positive for AE1/AE3, 34 beta E12 and p60). In July 2012, the patient was asymptomatic with no signs of local or systemic recurrence. She is regularly followed by the breast surgeons and clinical oncologists. DISCUSSION: Metaplastic breast carcinoma is associated with a faster local growth and a worse prognosis compared to ductal carcinomas. These metaplastic tumors show, in general, negative hormone receptors and Her2 negative on immunohistochemistry. In contrast, immunohistochemistry is often crucial in differentiating metaplastic carcinoma and primary sarcomas of the breast. The correct diagnosis of metaplastic carcinoma, differential diagnosis of sarcomas and invasive ductal carcinoma is important for proper treatment and prognosis. In relation to the metastatic potential, metaplastic tumors have higher rates of hematogenous metastases and lower rates of lymph node metastasis. There are no conclusive studies about the benefit of adjuvant chemo and radiation therapy, which makes surgery the main treatment.

Metaplastic carcinomas of breast are uncommon, representing 0.3% of invasive carcinomas of breast. We are reporting two cases of metaplastic carcinoma breast, one revealing rhabdomyoblastic and spindle cell differentiation and other revealing osteoclast like giant cells. Both were estrogen receptor, progesterone receptor and Her2u negative on immunohistochemistry. Early diagnosis of metaplastic carcinomas is essential as these tumors are usually triple negative and hence, do not respond to trans

Introduction: Metaplastic breast carcinoma is a heterogeneous group of infrequent invasive carcinomas with aggressive behavior. It presents differentiation from the neoplastic ductal epithelium to squamous and/or sarcomatous mesenchymal component, through the epithelial-mesenchymal transition process, and may present morphology of epithelioid and fusiform cells, with possible cartilage, bone, lipomatous, fibromatous, smooth muscle or skeletal muscle differentiation, among others. Most of the cases present the triple-negative immunohistochemical profile. Objective: To report three cases of metaplastic carcinomas, with an emphasis on clinical and pathological aspects, in addition to conducting a literature review on this topic. Methods: The three cases were registered in the internal search system for reference services in breast pathology in São Paulo, between 2012 and 2019. For literature review, the keywords metaplastic carcinoma, breast, cancer, review, breast cancer subtype and pathological and clinical outcomes were used in PubMed. We found 154 articles, of which 42 were selected for full reading, based on the abstract and established inclusion criteria. After this initial selection, these articles were read and reviewed; nine articles that did not meet the inclusion criteria were excluded. Discussion: Three cases of metaplastic carcinoma with similar immunohistochemical characteristics have been reported. The first case is that of a 40-year-old patient with the diagnosis of metaplastic carcinoma producing a chondroid matrix with liposarcomatous and osteosarcomatous differentiation. The second case is that of a 50-year-old patient who presented with the final diagnosis for a fusocellular metaplastic carcinoma with lymph node metastasis. Finally, the third case described is that of a 59-year-old patient, who presented metaplastic carcinoma with chondroid differentiation. Conclusion: Metaplastic carcinoma is a rare and aggressive type of breast cancer, in which most of the patients have shorter survival and worse prognosis in relation to the other subtypes. More studies are needed in order to determine a gold standard treatment for this disease.

Clinical Characteristics and Survival Outcomes of Metaplastic Breast Carcinoma Subtypes: A Retrospective Study.

Metaplastic breast carcinoma is a rare subtype of invasive carcinomas accounting to about 0.3% of all breast cancers. The World Health Organization (WHO) has classified metaplastic breast carcinoma (MBC) into the pure epithelial type and mixed epithelial and mesenchymal type. The epithelial type MBC subclassified into squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma with spindle cell differentiation; mixed type MBC is subclassified into carcinosarcoma and carcinoma with osseous and chondroid metaplasia. These carcinomas have aggressive clinical behavior and do not respond well to conventional adjuvant chemotherapy. We present a case of a 33-year-old female with the history of a breast lump for one year associated with the beginning of lactation. On consultation, the lump was misdiagnosed as Galactocele and neglected. Persistence of symptoms increase of pain and size of the lump brought the patient back in the surgical OPD (outpatient department) where she was examined and biopsied. The diagnosis of invasive ductal carcinoma was offered on the core biopsy. Postmastectomy the same was diagnosed as adenosquamous carcinoma with a malignant mesenchymal element. Keywords: Metaplastic breast carcinoma (MBC), adenosquamous carcinoma, metastatic sarcoma component Cite this Article Pramila Choudhary, Apoorvi Dubey, Amrit Raj Kalla, Anand Raj Kalla. Metaplastic Carcinoma Breast Masquerading as Galactocele—A Diagnostic Dilemma: A Rare Case. Research & Reviews: Journal of Oncology and Hematology. 2019; 8(1): 14–18p.

Metaplastic Breast Carcinoma (MBC) is very rare, and metaplastic carcinoma with osseous differentiation is even rarer. Here we report a case of metaplastic breast carcinoma with extensive osseous differentiation. A 65 years female presented with the complaint of lump left breast for the last 6 months. Fine Needle Aspiration Cytology (FNAC) suggested carcinoma breast. Modified radical mastectomy was performed. Histopathologically, the neoplasm consisted of invasive ductal carcinoma of no special type with an osseous metaplastic component and showed a direct transition from carcinoma to the osseous elements. It is necessary to distinguish the different types of metaplastic carcinomas and distinction between benign and malignant metaplastic (osteoid) elements should be taken into consideration.

BackgroundMetaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma.MethodsMastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate.ResultsHigh-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).ConclusionsHigh-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

Metaplastic breast carcinoma (MBC) has an incidence of <1% of all breast cancers and MBC with chondrosarcomatous differentiation is even more rare, <0.1% of all cases. The World Health Organization have classified MBC into pure epithelial-type and mixed epithelial and mesenchymal type. The epithelial-type MBC is sub-classified into squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma with spindle cell differentiation; mixed type MBC is sub-classified into carcinosarcoma and carcinoma with osseous and chondroid metaplasia. Metaplastic carcinomas of the breast are characterized by large tumour size and rapid growth, and they are usually estrogen receptor, progesterone receptor, and HER2/neu negative and tend to have a worse prognosis than other triple negative breast cancers. There is a noteworthy increased risk of tumour recurrence and a worse prognosis with MBC compared with invasive lobular carcinoma and infiltrating duct carcinoma. We report a case of metaplastic carcinoma with extensive chondroid differentiation that is chondrosarcoma and chondroid metaplasia along with classic infiltrating duct carcinoma with involvement of ipsilateral axillary lymph nodes.

BackgroundMetaplastic breast carcinoma is a rare aggressive malignant neoplasm. The purposes of this study are to review the pathologic features and clinical outcomes of metaplastic breast carcinoma compared to invasive ductal carcinoma and to evaluate the prognosis of metaplastic breast carcinoma.MethodsThe cases of 55 patients with metaplastic breast carcinomapresenting between 1991 and 2006 were analyzed and compared to the cases of 767 age-matched patients with invasive ductal carcinoma from the same time period.ResultsThe group of patients with metaplastic breast carcinoma presented with a larger tumor size, lower lymph node involvement, higher percentage of triple-negative (estrogen receptor-, progesterone receptor- and human epidermal growth factor receptor-2-negative) cases, and Ki-67 over-expression compared with the group of patients with invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Patients in the metaplastic breast carcinoma group tended to have more local (often chest wall) recurrences (P = 0.038) and distant (often lung) metastases (P = 0.001) than those in the invasive ductal carcinomas group. The prognosis of metaplastic breast carcinoma was poorer than that of invasive ductal carcinoma and triple-negative invasive ductal carcinomas; the 5-year overall survival rate was 54.5% in metaplastic breast carcinoma versus 85.1% in invasive ductal carcinoma, and 73.3% in triple-negative invasive ductal carcinomas (P <0.001). The 5-year disease-free survival rate was 45.5% in metaplastic breast carcinoma versus 71.2% in invasive ductal carcinoma, and 60.3% in triple-negative invasive ductal carcinomas (P <0.001). Multivariate analysis revealed tumor size larger than 5.0 cm, lymph node involvement and Ki-67≥14% were significantly related to 5-year overall survival (P = 0.010; P = 0.010; P = 0.035) and 5-year disease-free survival (P = 0.020; P = 0.018; P = 0.049).ConclusionsMetaplastic breast carcinoma shows a poorer prognosis than both invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Tumor size larger than 5.0 cm, lymph node involvement and Ki-67 ≥14% indicate a poor prognosis in patients with metaplastic breast carcinoma.

Introduction Metaplastic breast carcinoma is a rare special type of breast cancer, which has distinguished clinical characteristics. We aimed to evaluate the clinicopathological features of metaplastic breast carcinoma compared with nonspecific invasive breast carcinoma and study the prognosis of metaplastic breast carcinoma. Methods We reviewed metaplastic breast carcinoma cases (n = 37) from January 2000 to December 2021 and nonspecific invasive breast carcinoma cases (n = 433) from January 2019 to December 2020 extracted from our institution retrospectively. The following variables were recorded, including the patients' general information, complications, T stage, expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular subtyping, lymph node status, skin or chest wall involvement, vessel carcinoma embolus, therapy modality (surgical treatments, chemotherapy, and radiotherapy), and survival. Results Patients with metaplastic breast carcinoma had more advanced disease than patients with nonspecific invasive breast carcinoma (T stage: P=0.0011). A greater proportion of metaplastic breast carcinoma presented with triple-negative breast cancer than nonspecific invasive breast carcinoma (79.41% vs. 12.47%, P ≤ 0.001). Our study showed that the skin or chest wall invasion was more frequent in metaplastic breast carcinoma patients (11.76% vs. 1.62%, P=0.005). The 5-year survival rate for metaplastic breast carcinoma patients was 57.66% (95% CI: 0.3195∼0.7667). No local recurrence was observed while distant metastasis occurred in 33.33% of patients with metaplastic breast carcinoma. Death due to disease occurred in 24.24% of patients with metaplastic breast carcinoma. Conclusion The majority of metaplastic breast carcinoma patients had more advanced disease and triple-negative disease than nonspecific invasive breast carcinoma patients. Also, metaplastic breast carcinoma patients had frequent skin or chest wall invasion and a high rate of distant metastasis and mortality.

Metaplastic breast carcinoma: a clinical-pathologic study of 97 cases with subset analysis of response to neoadjuvant chemotherapy

Metaplastic carcinoma is a rare form of breast cancer occurring in less than 1%. It constitutes a distinct aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition towards spindle, chondroid or osseous cell type. Osseous metaplasia is an extremely rare variant of metaplastic breast carcinoma. We, therefore, present this case of a 45yr old woman with metaplastic breast carcinoma with osteosarcomatous differentiation and lung metastasis due to this rare combination. This patient had a massive recurrent tumour within two weeks of mastectomy. Keywords: Metaplastic, Breast, Cancer, osteosarcomatous

Metaplastic carcinoma (carcinoma with pseudosarcomatous metaplasia) of the breast are high-grade carcinomas in which much of the tumor undergoes metaplastic change producing a pseudosarcomatous pattern. We report a case of metaplastic breast carcinoma (MBC) in whom fine-needle aspiration (FNA) cytology was performed with later histological confirmation. The lesion affected a 68-yr-old woman, with a tumor measuring 6.4 x 5.3 cm well demarcated mass located in the upper outer quadrant of the right breast. FNA cytology revealed a variety of markedly atypical cells, mainly spindle-shaped, and mitotic figures sporadically distributed against a severely necrotic background. Atypical chondrocytes were observed against a background of myxomatous substance that displayed metachromasia with May-Giemsa stain that resembled chondrosarcoma cells. Clusters of markedly atypical carcinoma cells that exhibited epithelial junctions were also seen, and immunostaining confirmed the presence of both mesenchyme-marker-positive sarcomatous and epithelial-marker-positive carcinoma cells. Careful attention to the precise cellular composition such as sarcomatous cells, chondrosarcomatous cells and carcinoma cells should allow the recognition of these neoplasms. Therefore, MBC seems to be very a characteristic tumor in which accurate cellular diagnosis may be achieved by FNA cytology.

Metaplastic breast carcinoma is a rare type of breast carcinoma, and there are limited data about the magnetic resonance imaging (MRI) findings of metaplastic carcinoma. This study evaluates the MRI characteristics and prognostic outcomes across metaplastic carcinoma subtypes. In this retrospective cohort study, a total of 29 patients with histologically confirmed metaplastic carcinoma from 2011 to 2019 were enrolled. Clinical, pathological, and follow-up data, focusing on disease-free (DFS) and overall survival (OS), are recorded. Breast MRI findings were analyzed and categorized based on BI-RADS 5th edition. Among the participants, 19 had squamous carcinoma, 8 had metaplastic carcinoma with mesenchymal differentiation, and 2 had unclassified subtypes. The most common findings were a solitary mass (75.8%), high T2 signal (51.7%), and heterogenous enhancement (65.5%) with a washout kinetic curve (86.2%). The apparent diffusion coefficient (ADC) values in the metaplastic carcinoma with mesenchymal differentiation group were significantly higher (mean 1.83 +/- 0.50 x 10-3 mm2/s) in comparison with the squamous carcinoma group (mean 1.12 +/- 0.21 x 10-3 mm2/s). The cut-off point of the ADC value was 1.53x10-3 mm2/s, with a sensitivity of 71.4% and a specificity of 100% (AUC = 0.937). The five-year DFS and OS rates were 63% and 79% across the board, 78% and 89.5% in the squamous group, and 50% and 53% in the mesenchymal differentiation group, respectively. Metaplastic breast carcinoma is a diverse and aggressive malignancy with variable prognosis. Our findings indicate that mesenchymal differentiation is characterized by higher ADC values and correlates with a worse prognosis.